Interleukin-6: a villain in the drama of pancreatic cancer development and progression

Hepatobiliary Pancreat Dis Int. 2014 Aug;13(4):371-80. doi: 10.1016/s1499-3872(14)60259-9.

Abstract

Background: Pancreatic ductal adenocarcinoma (PDAC) is a devastating malignancy with a poor prognosis and little treatment options. The development and progression of the disease is fostered by inflammatory cells and cytokines. One of these cytokines is interleukin-6 (IL-6), which plays an important role in a wide range of biologic activities.

Data sources: A systematic search of PubMed was performed to identify relevant studies using key words such as interleukin-6, inflammatory cytokines, inflammation and pancreatic cancer or PDAC. Articles related to IL-6 and pancreatic cancer were systematically reviewed.

Results: IL-6 is elevated in the serum of pancreatic cancer patients and correlates with cachexia, advanced tumor stage and poor survival. Its expression is enhanced by hypoxia and proteins involved in pancreatic cancer development like Kras, mesothelin or ZIP4. IL-6 in turn contributes to the generation of a pro-tumorigenic microenvironment and is probably involved in angiogenesis and metastasis. In experimental mouse models of PDAC, IL-6 was important for the development and progression of precursor lesions.

Conclusion: IL-6 emerges as a key player in pancreatic cancer development and progression, and hence should be considered as a new therapeutic target.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / metabolism*
  • Carcinoma, Pancreatic Ductal / drug therapy
  • Carcinoma, Pancreatic Ductal / immunology
  • Carcinoma, Pancreatic Ductal / metabolism*
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Transformation, Neoplastic / immunology
  • Cell Transformation, Neoplastic / metabolism
  • Disease Progression
  • Drug Design
  • Humans
  • Inflammation Mediators / metabolism*
  • Interleukin-6 / antagonists & inhibitors
  • Interleukin-6 / metabolism*
  • Molecular Targeted Therapy
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / immunology
  • Pancreatic Neoplasms / metabolism*
  • Pancreatic Neoplasms / pathology
  • Precancerous Conditions / drug therapy
  • Precancerous Conditions / immunology
  • Precancerous Conditions / metabolism*
  • Precancerous Conditions / pathology
  • Signal Transduction* / drug effects
  • Tumor Microenvironment

Substances

  • Antineoplastic Agents
  • Biomarkers, Tumor
  • IL6 protein, human
  • Inflammation Mediators
  • Interleukin-6